This investigation is concerned with the biologic basis at the cellular and molecular levels for cardiomyopathy associated with the use of chemotherapeutic agent adriamycin and its related anthracycline analogues. The durgs have proven extremely valuable in the treatment of several malignancies; however, maintenance therapy may be contraindicated because of cumulative cardiotoxicity of unknown etiology. Mammalian myocardial cells in culture are used as a model system to study selected processes in cells treated with adriamycin and related drugs in an attempt to localize the site and the mechanism of drug action. The antibiotic activity of andriamycin may involve the intercalation into DNA with subsequent inhibition of DNA synthesis, but it is not clear what mechanism is involved in cardiotoxicity since adult myocardium is not characterized by rapidly proliferating cells. The effect of adriamycin on the physical integrity of DNA will be examined in rat heart cells grown in culture in an attempt to focus upon the molecular basis for adriamycin induced cardiotoxicity. In related cell free studies, laser Raman spectroscopy will be used to examine adriamycin-DNA complexes for the purpose of determining the moieties involved in intercalative and ionic modes of drug-DNA binding. An assay system will be developed to identify and purify classes of heart cell enzymes responsible for causing DNA fragmentation in the presence of adriamycin. The effect of adriamycin on the fidelity of DNA synthesis will be determined. Information generated from this study will be of importance in elucidating the mechanism of action of the drugs and their usefulness in maintenance therapy and could add to the elucidation of the poorly understood primary myocardiopathies.